Journal of Zhejiang University SCIENCE B最新文献

Sentinel lymph nodes (SLNs) are the first station of lymph nodes that extend from the breast tumor to the axillary lymphatic drainage. The pathological status of these LNs can predict that of the entire axillary lymph node. Therefore, the accurate identification of SLNs is necessary for sentinel lymph node biopsy (SLNB) to replace axillary lymph node dissection (ALND). The quality of life and prognosis of breast cancer patients are related to proper surgical treatment after the precise identification of SLNs. Some of the SLN tracers that have been identified include radioisotope, nano-carbon, indocyanine green (ICG), and methylene blue (MB). However, these tracers have certain limitations, such as pigmentation, radiation dangers, and the requirement for costly detection equipment. Ultrasound contrast agents (UCAs) have good specificity and sensitivity, and thus can compensate for some shortcomings of the mentioned tracers. This technique is also being applied to SLNB in patients with breast cancer, and can even provide an initial judgment on SLN status. Contrast-enhanced ultrasound (CEUS) has the advantages of high distinguishability, simple operation, no radiation harm, low cost, and accurate localization; therefore, it is expected to replace the traditional biopsy methods. In addition, it can significantly enhance the accuracy of SLN localization and shorten the operation time.

This study aims to investigate the impact of hepatocyte nuclear factor 1β (HNF1b) on macrophage sortilin-mediated lipid metabolism and aortic atherosclerosis and explore the role of the flavone of Polygonatum odoratum (PAOA-flavone)-promoted small ubiquitin-related modifier (SUMO) modification in the atheroprotective efficacy of HNF1b. HNF1b was predicted to be a transcriptional regulator of sortilin expression via bioinformatics, dual-luciferase reporter gene assay, and chromatin immunoprecipitation. HNF1b overexpression decreased sortilin expression and cellular lipid contents in THP-1 macrophages, leading to a depression in atherosclerotic plaque formation in low-density lipoprotein (LDL) receptor-deficient (LDLR^-/-) mice. Multiple SUMO1-modified sites were identified on the HNF1b protein and co-immunoprecipitation confirmed its SUMO1 modification. The SUMOylation of HNF1b protein enhanced the HNF1b-inhibited effect on sortilin expression and reduced lipid contents in macrophages. PAOA-flavone treatment promoted SUMO-activating enzyme subunit 1 (SAE1) expression and SAE1-catalyzed SUMOylation of the HNF1b protein, which prevented sortilin-mediated lipid accumulation in macrophages and the formation of atherosclerotic plaques in apolipoprotein E-deficient (ApoE^-/-) mice. Interference with SAE1 abrogated the improvement in lipid metabolism in macrophage cells and atheroprotective efficacy in vivo upon PAOA-flavone administration. In summary, HNF1b transcriptionally suppressed sortilin expression and macrophage lipid accumulation to inhibit aortic lipid deposition and the development of atherosclerosis. This anti-atherosclerotic effect was enhanced by PAOA-flavone-facilitated, SAE1-catalyzed SUMOylation of the HNF1b protein.

Silk fibroin (SF) as a natural biopolymer has become a popular material for biomedical applications due to its minimal immunogenicity, tunable biodegradability, and high biocompatibility. Nowadays, various techniques have been developed for the applications of SF in bioengineering. Most of the literature reviews focus on the SF-based biomaterials and their different forms of applications such as films, hydrogels, and scaffolds. SF is also valuable as a coating on other substrate materials for biomedicine; however, there are few reviews related to SF-coated biomaterials. Thus, in this review, we focused on the surface modification of biomaterials using SF coatings, demonstrated their various preparation methods on substrate materials, and introduced the latest procedures. The diverse applications of SF coatings for biomedicine are discussed, including bone, ligament, skin, mucosa, and nerve regeneration, and dental implant surface modification. SF coating is conducive to inducing cell adhesion and migration, promoting hydroxyapatite (HA) deposition and matrix mineralization, and inhibiting the Notch signaling pathway, making it a promising strategy for bone regeneration. In addition, SF-coated composite scaffolds can be considered prospective candidates for ligament regeneration after injury. SF coating has been proven to enhance the mechanical properties of the substrate material, and render integral stability to the dressing material during the regeneration of skin and mucosa. Moreover, SF coating is a potential strategy to accelerate nerve regeneration due to its dielectric properties, mechanical flexibility, and angiogenesis promotion effect. In addition, SF coating is an effective and popular means for dental implant surface modification to promote osteogenesis around implants made of different materials. Thus, this review can be of great benefit for further improvements in SF-coated biomaterials, and will undoubtedly contribute to clinical transformation in the future.

Multicellular spheroids, which mimic the natural organ counterparts, allow the prospect of drug screening and regenerative medicine. However, their application is hampered by low processing efficiency or limited scale. This study introduces an efficient method to drive rapid multicellular spheroid formation by a cellulose nanofibril matrix. This matrix enables the facilitated growth of spheroids (within 48 h) through multiple cell assembly into size-controllable aggregates with well-organized physiological microstructure. The efficiency, dimension, and conformation of the as-formed spheroids depend on the concentration of extracellular nanofibrils, the number of assembled cells, and the heterogeneity of cell types. The above strategy allows the robust formation mechanism of compacted tumoroids and hepatocyte spheroids.

Recent advances in lymphoma treatment have significantly improved the survival of patients; however, the current approaches also have varying side effects. To overcome these, it is critical to implement individualized treatment according to the patient's condition. Therefore, the early identification of high-risk groups and targeted treatment are important strategies for prolonging the survival time and improving the quality of life of patients. Interim positron emission tomography-computed tomography (PET-CT) has a high prognostic value, which can reflect chemosensitivity and identify patients for whom treatment may fail under this regimen. To date, many prospective clinical studies on interim PET (iPET)‍-adapted therapy have been conducted. In this review, we focus on the treatment strategies entailed in these studies, as well as the means and timing of iPET assessment, with the aim of exploring the efficacy and existing issues regarding iPET-adapted treatment. It is expected that the improved use of PET-CT examination can facilitate treatment decision-making to identify precise treatment options.

Lung cancer remains the leading cause of cancer deaths worldwide and is the most common cancer in males. Immune-checkpoint inhibitors (ICIs) that target programmed cell death protein-1 (PD-1) or programmed cell death-ligand 1 (PD-L1) have achieved impressive efficacy in the treatment of non-small-cell lung cancer (NSCLC) (Pardoll, 2012; Champiat et al., 2016; Gao et al., 2022). Although ICIs are usually well tolerated, they are often accompanied by immune-related adverse events (irAEs) (Doroshow et al., 2019). Non-specific activation of the immune system produces off-target immune and inflammatory responses that can affect virtually any organ or system (O'Kane et al., 2017; Puzanov et al., 2017). Compared with adverse events caused by chemotherapy, irAEs are often characterized by delayed onset and prolonged duration and can occur in any organ at any stage of treatment, including after cessation of treatment (Puzanov et al., 2017; von Itzstein et al., 2020). They range from rash, pneumonitis, hypothyroidism, enterocolitis, and autoimmune hepatitis to cardiovascular, hematological, renal, neurological, and ophthalmic irAEs (Nishino et al., 2016; Kumar et al., 2017; Song et al., 2020). Hence, we conducted a retrospective study to identify validated factors that could predict the magnitude of the risk of irAEs in patients receiving PD-1/PD-L1 inhibitors; our approach was to analyze the correlation between the clinical characteristics of patients at the start of treatment and relevant indicators such as hematological indices and the risk of developing irAEs. Then, we developed an economical, practical, rapid, and simple model to assess the risk of irAEs in patients receiving ICI treatment, as early as possible.

Over the past decade, dramatic progress has been made in dental research areas involving laser therapy. The photobiomodulatory effect of laser light regulates the behavior of periodontal tissues and promotes damaged tissues to heal faster. Additionally, photobiomodulation therapy (PBMT), a non-invasive treatment, when applied in orthodontics, contributes to alleviating pain and reducing inflammation induced by orthodontic forces, along with improving tissue healing processes. Moreover, PBMT is attracting more attention as a possible approach to prevent the incidence of orthodontically induced inflammatory root resorption (OIIRR) during orthodontic treatment (OT) due to its capacity to modulate inflammatory, apoptotic, and anti-antioxidant responses. However, a systematic review revealed that PBMT has only a moderate grade of evidence-based effectiveness during orthodontic tooth movement (OTM) in relation to OIIRR, casting doubt on its beneficial effects. In PBMT-assisted orthodontics, delivering sufficient energy to the tooth root to achieve optimal stimulation is challenging due to the exponential attenuation of light penetration in periodontal tissues. The penetration of light to the root surface is another crucial unknown factor. Both the penetration depth and distribution of light in periodontal tissues are unknown. Thus, advanced approaches specific to orthodontic application of PBMT need to be established to overcome these limitations. This review explores possibilities for improving the application and effectiveness of PBMT during OTM. The aim was to investigate the current evidence related to the underlying mechanisms of action of PBMT on various periodontal tissues and cells, with a special focus on immunomodulatory effects during OTM.